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Taxane Regimens
Letter to the Editor Re: Lymphopenia Associated With Adjuvant Anthracycline/Taxane Regimens We read with interest the excellent article by Tolaney et al, published in the August 2008 edition of Clinical Breast Cancer: “Lymphopenia Associated With Adjuvant Anthracycline/Taxane Regimens,” which provides interesting and much-needed data on lymphopenia in women receiving adjuvant chemotherapy for breast cancer.1 A recent case from our institution highlights some important related issues. A 68-year-old woman presented with neutropenic fever while receiving adjuvant chemotherapy for T1 N0 M0 estrogen receptor/progesterone receptor–negative, HER2-negative invasive ductal breast carcinoma. She presented on day 8 after cycle 2 of dose-dense doxorubicin/cyclophosphamide/ paclitaxel (ACT) with pegfilgrastim support. She had a dry cough, was dyspneic on exertion, and was commenced on piperacillin/tazobactam with gentamicin as standard local protocol. Three days later, amphotericin B was added for persistent pyrexia. She failed to respond, however, becoming increasingly dyspneic and desaturating markedly on exertion. Pneumocystis carinii pneumonia (PCP) was suspected, and primaquine, clindamycin, and prednisolone were commenced in light of a previously well-documented sulfa allergy. A computed tomography scan of the thorax revealed diffuse, bilateral, ground-glass changes consistent with PCP. Bronchoalveolar lavage was nondiagnostic, as has been previously demonstrated in other immunocompromised patients with PCP who, in contrast to HIV-positive patients, have lower organism burden.2 Clinically, she improved significantly within 24 hours of institution of PCP treatment, and a presumptive diagnosis of PCP was made. Despite resolution of symptoms and good exercise tolerance, she continued to desaturate on pulse oximetry. However, arterial blood gas measurement revealed normal PaO2, raising the possibility of primaquine-associated methemoglobinemia. Her methemoglobin level was 13%, confirming the diagnosis. Primaquine was discontinued, and both her methemoglobin level and pulse oximetry measurements normalized.
DOI: 10.3816/CBC.2009.n.045
Address for correspondence: Karen Cadoo, MB, BCh, Medical Oncology, The Mater Misericordiae University Hospital, Medical Oncology, Eccles Street, Dublin, Dublin 7 Ireland E-mail: [email protected]
We agree with Tolaney et al that lymphocyte depletion in this population places these patients at risk for opportunistic infection. It is interesting that their study found similar rates of grade 3/4 lymphopenia in the cohorts receiving dose-dense and 3-weekly ACT. They demonstrated that the lowest median absolute lymphocyte count was around cycle 5, likely reflecting steroid premedication with commencement of paclitaxel, a theory reinforced by the finding that the group receiving albumin-bound paclitaxel had significantly lower rates of lymphopenia. As with the women previously described by Tolaney et al,3 our patient received only intermittent steroids as antiemetics. Perhaps PCP prophylaxis should be considered from commencement of chemotherapy to protect from the risk posed by prolonged lymphopenia. Additionally, our case illustrates that further surveillance and vigilance is required when treatment has been instituted. A number of the drugs used in management of PCP, commonly dapsone and primaquine, have been associated with methemoglobinemia,4 which can be life threatening. Importantly, arterial blood gas might provide falsely reassuring oxygen saturations. As with our patient, pulse oximetry, however, will demonstrate lower saturations than that found on the arterial blood gas measurement, leading to a “saturation gap” that should provoke measurement of methemoglobin. Given the poorly understood risk factors for PCP and the absence of data regarding prophylaxis in this group, we feel that this is an area that warrants further investigation.
Disclosures The authors report no relevant financial conflicts of interest.
Karen Cadoo, Meave Lowery, John McCaffrey References 1. Tolaney SM, Najita J, Winer EP, et al. Lymphopenia associated with adjuvant anthracycline/ taxane regimens. Clin Breast Cancer 2008; 8:352-6. 2. Jacobs JA, Dieleman MM, Cornelissen EI, et al. Bronchoalveolar lavage fluid cytology in patients with Pneumocystis carinii pneumonia. Acta Cytol 2001; 45:317-26. 3. Tolaney SM, Partridge AH, Sheib RG, et al. Pneumocystis carinii pneumonia during dose-dense chemotherapy for breast cancer. J Clin Oncol 2006; 24:5330-1. 4. Beutler E. Methemoglobinemia and other causes of cyanosis. In: Beutler E, Lichtman MA, Coller B, Kipps TJ, eds. Williams' Hematology. 5th ed. New York: McGraw-Hill; 1995:654.
This summary may include the discussion of investigational and/or unlabeled uses of drugs and/or devices that may not be approved by the FDA. Electronic forwarding or copying is a violation of US and International Copyright Laws. Authorization to photocopy items for internal or personal use, or the internal or personal use of specific clients, is granted by CIG Media Group, LP, ISSN #1526-8209, provided the appropriate fee is paid directly to Copyright Clearance Center, 222 Rosewood Drive, Danvers, MA 01923 USA. www.copyright.com 978-750-8400.
262
| Clinical Breast Cancer
November 2009
DOI: 10.3816/CBC.2009.n.045
Address for correspondence: Karen Cadoo, MB, BCh, Medical Oncology, The Mater Misericordiae University Hospital, Medical Oncology, Eccles Street, Dublin, Dublin 7 Ireland E-mail: [email protected]
We agree with Tolaney et al that lymphocyte depletion in this population places these patients at risk for opportunistic infection. It is interesting that their study found similar rates of grade 3/4 lymphopenia in the cohorts receiving dose-dense and 3-weekly ACT. They demonstrated that the lowest median absolute lymphocyte count was around cycle 5, likely reflecting steroid premedication with commencement of paclitaxel, a theory reinforced by the finding that the group receiving albumin-bound paclitaxel had significantly lower rates of lymphopenia. As with the women previously described by Tolaney et al,3 our patient received only intermittent steroids as antiemetics. Perhaps PCP prophylaxis should be considered from commencement of chemotherapy to protect from the risk posed by prolonged lymphopenia. Additionally, our case illustrates that further surveillance and vigilance is required when treatment has been instituted. A number of the drugs used in management of PCP, commonly dapsone and primaquine, have been associated with methemoglobinemia,4 which can be life threatening. Importantly, arterial blood gas might provide falsely reassuring oxygen saturations. As with our patient, pulse oximetry, however, will demonstrate lower saturations than that found on the arterial blood gas measurement, leading to a “saturation gap” that should provoke measurement of methemoglobin. Given the poorly understood risk factors for PCP and the absence of data regarding prophylaxis in this group, we feel that this is an area that warrants further investigation.
Disclosures The authors report no relevant financial conflicts of interest.
Karen Cadoo, Meave Lowery, John McCaffrey References 1. Tolaney SM, Najita J, Winer EP, et al. Lymphopenia associated with adjuvant anthracycline/ taxane regimens. Clin Breast Cancer 2008; 8:352-6. 2. Jacobs JA, Dieleman MM, Cornelissen EI, et al. Bronchoalveolar lavage fluid cytology in patients with Pneumocystis carinii pneumonia. Acta Cytol 2001; 45:317-26. 3. Tolaney SM, Partridge AH, Sheib RG, et al. Pneumocystis carinii pneumonia during dose-dense chemotherapy for breast cancer. J Clin Oncol 2006; 24:5330-1. 4. Beutler E. Methemoglobinemia and other causes of cyanosis. In: Beutler E, Lichtman MA, Coller B, Kipps TJ, eds. Williams' Hematology. 5th ed. New York: McGraw-Hill; 1995:654.
This summary may include the discussion of investigational and/or unlabeled uses of drugs and/or devices that may not be approved by the FDA. Electronic forwarding or copying is a violation of US and International Copyright Laws. Authorization to photocopy items for internal or personal use, or the internal or personal use of specific clients, is granted by CIG Media Group, LP, ISSN #1526-8209, provided the appropriate fee is paid directly to Copyright Clearance Center, 222 Rosewood Drive, Danvers, MA 01923 USA. www.copyright.com 978-750-8400.
262
| Clinical Breast Cancer
November 2009